Differential impact of age, sex steroid hormones, and obesity on basal versus pulsatile growth hormone secretion in men as assessed in an ultrasensitive chemiluminescence assay

Johannes D Veldhuis, A. Y. Liem, S. South, A. Weltman, J. Weltman, D. A. Clemmons, R. Abbott, T. Mulligan, M. L. Johnson, S. Pincus, M. Straume, A. Iranmanesh

Research output: Contribution to journalArticle

342 Citations (Scopus)

Abstract

A chemiluminescence-based GH assay with 30- to 100-fold increased sensitivity recently disclosed combined basal and pulsatile GH secretion in men. However, how age, sex steroid hormones, and obesity singly and jointly influence the basal vs. pulsatile modes of GH release is not known. We used the foregoing assay (detection threshold, 0.002-0.005 μg/L) and high sensitivity and specificity (≥90% each) deconvolution analysis to quantitate basal and pulsatile GH secretion from 24-h serum GH concentration profiles in 26 healthy lean and obese men, whose ages spanned 18-63 yr and whose percentage body fat ranged from 12-47%. Concentrations of serum insulin-like growth factor I (IGF-I), IGF-I-binding protein-1 (IGFBP-1), and IGFBP-3 were related to specific measures of basal or pulsatile GH release. We observed that mean (24-h) serum GH concentrations embraced a 140-fold range from 0.013-1.8 μg/L and were related negatively to age (r = -0.50; P < 0.01), percentage body fat (r = -0.620; P < 0.01), and their interaction (r = - 0.610; P < 0.01). In contrast, testosterone was a robustly positive statistical determinant of mean serum GH values (r = 0.628; P = 0.0006). Stepwise multivariate regression analysis disclosed that percentage body fat alone and jointly with the serum testosterone concentration controlled, respectively, 38% and 50% of the total variability in GH levels (P = 0.0013 and P = 0.0008). As assessed by deconvolution analysis, GH secretory burst mass was negatively related to percentage body fat (r = -0.621; P < 0.01) and positively to serum testosterone (r = 0.529; P = 0.0054). The calculated half-life of GH correlated positively with serum estradiol (r = 0.447; P = 0.032), and negatively with percentage body fat (r = -0.437; P = 0.048). Basal GH secretion rates were negatively related to serum estradiol (r = - 0.485; P = 0.016). In contrast, GH secretory burst frequency and duration were unrelated to age, percentage body fat, or sex steroids. The fraction of total GH secreted in bursts was negatively correlated with the body mass index (r = -0.540; P < 0.01). Serum IGF-I concentrations were positively related to total pulsatile GH secretion (r = 0.690; P = 0.0011) and negatively to age (r = -0.597; P = 0.007) and percentage body fat (r = - 0.611; P = 0.009). Serum IGFBP-3 was inversely proportional to the basal GH secretion rate (r = -0.467; P = 0.044). In contrast, IGFBP-1 concentrations correlated positively with GH secretory burst mass (r = 0.674; P = 0.0016) as well as basal GH secretion (r = 0.519; P = 0.023), and negatively with age, and percentage body fat and their interactions (absolute r values = 0.517- 0.653; P ≤ 0.021). The serial orderliness of GH release, as assessed by a novel approximate entropy (ApEn) statistic, revealed decreased orderliness (higher ApEn) of GH release with increasing age (r = 0.482; P = 0.019) and adiposity (r = 0.505; P = 0.014). In contrast, the patterned regularity of GH release rose (lower ApEn) with higher serum testosterone concentrations (r = -0.405; P = 0.048). In summary, we infer that in healthy men, 1) basal and pulsatile GH secretion may be regulated differentially by estradiol and testosterone, respectively; 2) basal and pulsatile GH release may influence serum IGF-I, IGFBP-3, and IGFBP-1 concentrations in distinct ways; and 3) the serial regularity or orderliness of GH release is negatively related to age and obesity, but positively to the serum androgen concentration. Accordingly, we hypothesize that 1) distinct neuroendocrine regulatory mechanisms govern basal vs. pulsatile GH secretion; 2) GH target tissue responses, as reflected by serum IGF-I, IGFBP-3, and IGFBP-1 concentrations, are controlled by the specific temporal mode (basal vs. pulsatile) of GH release; and 3) the reproducibility of GH release patterns (estimated by an approximate entropy statistic) in normal men is modulated by key physiological variables (age, body composition, and serum testosterone concentrations), which, therefore, probably act to coordinate hypothalamic somatostatin and GHRH secretion temporally.

Original languageEnglish (US)
Pages (from-to)3209-3222
Number of pages14
JournalJournal of Clinical Endocrinology and Metabolism
Volume80
Issue number11
StatePublished - 1995
Externally publishedYes

Fingerprint

Chemiluminescence
Gonadal Steroid Hormones
Luminescence
Insulin-Like Growth Factor I
Growth Hormone
Assays
Obesity
Fats
Testosterone
Insulin-Like Growth Factor Binding Protein 3
Serum
Adipose Tissue
Carrier Proteins
Entropy
Insulin-Like Growth Factor Binding Protein 1
Estradiol
Deconvolution
Statistics
Somatostatin
Regression analysis

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Differential impact of age, sex steroid hormones, and obesity on basal versus pulsatile growth hormone secretion in men as assessed in an ultrasensitive chemiluminescence assay. / Veldhuis, Johannes D; Liem, A. Y.; South, S.; Weltman, A.; Weltman, J.; Clemmons, D. A.; Abbott, R.; Mulligan, T.; Johnson, M. L.; Pincus, S.; Straume, M.; Iranmanesh, A.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 80, No. 11, 1995, p. 3209-3222.

Research output: Contribution to journalArticle

Veldhuis, JD, Liem, AY, South, S, Weltman, A, Weltman, J, Clemmons, DA, Abbott, R, Mulligan, T, Johnson, ML, Pincus, S, Straume, M & Iranmanesh, A 1995, 'Differential impact of age, sex steroid hormones, and obesity on basal versus pulsatile growth hormone secretion in men as assessed in an ultrasensitive chemiluminescence assay', Journal of Clinical Endocrinology and Metabolism, vol. 80, no. 11, pp. 3209-3222.
Veldhuis, Johannes D ; Liem, A. Y. ; South, S. ; Weltman, A. ; Weltman, J. ; Clemmons, D. A. ; Abbott, R. ; Mulligan, T. ; Johnson, M. L. ; Pincus, S. ; Straume, M. ; Iranmanesh, A. / Differential impact of age, sex steroid hormones, and obesity on basal versus pulsatile growth hormone secretion in men as assessed in an ultrasensitive chemiluminescence assay. In: Journal of Clinical Endocrinology and Metabolism. 1995 ; Vol. 80, No. 11. pp. 3209-3222.
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abstract = "A chemiluminescence-based GH assay with 30- to 100-fold increased sensitivity recently disclosed combined basal and pulsatile GH secretion in men. However, how age, sex steroid hormones, and obesity singly and jointly influence the basal vs. pulsatile modes of GH release is not known. We used the foregoing assay (detection threshold, 0.002-0.005 μg/L) and high sensitivity and specificity (≥90{\%} each) deconvolution analysis to quantitate basal and pulsatile GH secretion from 24-h serum GH concentration profiles in 26 healthy lean and obese men, whose ages spanned 18-63 yr and whose percentage body fat ranged from 12-47{\%}. Concentrations of serum insulin-like growth factor I (IGF-I), IGF-I-binding protein-1 (IGFBP-1), and IGFBP-3 were related to specific measures of basal or pulsatile GH release. We observed that mean (24-h) serum GH concentrations embraced a 140-fold range from 0.013-1.8 μg/L and were related negatively to age (r = -0.50; P < 0.01), percentage body fat (r = -0.620; P < 0.01), and their interaction (r = - 0.610; P < 0.01). In contrast, testosterone was a robustly positive statistical determinant of mean serum GH values (r = 0.628; P = 0.0006). Stepwise multivariate regression analysis disclosed that percentage body fat alone and jointly with the serum testosterone concentration controlled, respectively, 38{\%} and 50{\%} of the total variability in GH levels (P = 0.0013 and P = 0.0008). As assessed by deconvolution analysis, GH secretory burst mass was negatively related to percentage body fat (r = -0.621; P < 0.01) and positively to serum testosterone (r = 0.529; P = 0.0054). The calculated half-life of GH correlated positively with serum estradiol (r = 0.447; P = 0.032), and negatively with percentage body fat (r = -0.437; P = 0.048). Basal GH secretion rates were negatively related to serum estradiol (r = - 0.485; P = 0.016). In contrast, GH secretory burst frequency and duration were unrelated to age, percentage body fat, or sex steroids. The fraction of total GH secreted in bursts was negatively correlated with the body mass index (r = -0.540; P < 0.01). Serum IGF-I concentrations were positively related to total pulsatile GH secretion (r = 0.690; P = 0.0011) and negatively to age (r = -0.597; P = 0.007) and percentage body fat (r = - 0.611; P = 0.009). Serum IGFBP-3 was inversely proportional to the basal GH secretion rate (r = -0.467; P = 0.044). In contrast, IGFBP-1 concentrations correlated positively with GH secretory burst mass (r = 0.674; P = 0.0016) as well as basal GH secretion (r = 0.519; P = 0.023), and negatively with age, and percentage body fat and their interactions (absolute r values = 0.517- 0.653; P ≤ 0.021). The serial orderliness of GH release, as assessed by a novel approximate entropy (ApEn) statistic, revealed decreased orderliness (higher ApEn) of GH release with increasing age (r = 0.482; P = 0.019) and adiposity (r = 0.505; P = 0.014). In contrast, the patterned regularity of GH release rose (lower ApEn) with higher serum testosterone concentrations (r = -0.405; P = 0.048). In summary, we infer that in healthy men, 1) basal and pulsatile GH secretion may be regulated differentially by estradiol and testosterone, respectively; 2) basal and pulsatile GH release may influence serum IGF-I, IGFBP-3, and IGFBP-1 concentrations in distinct ways; and 3) the serial regularity or orderliness of GH release is negatively related to age and obesity, but positively to the serum androgen concentration. Accordingly, we hypothesize that 1) distinct neuroendocrine regulatory mechanisms govern basal vs. pulsatile GH secretion; 2) GH target tissue responses, as reflected by serum IGF-I, IGFBP-3, and IGFBP-1 concentrations, are controlled by the specific temporal mode (basal vs. pulsatile) of GH release; and 3) the reproducibility of GH release patterns (estimated by an approximate entropy statistic) in normal men is modulated by key physiological variables (age, body composition, and serum testosterone concentrations), which, therefore, probably act to coordinate hypothalamic somatostatin and GHRH secretion temporally.",
author = "Veldhuis, {Johannes D} and Liem, {A. Y.} and S. South and A. Weltman and J. Weltman and Clemmons, {D. A.} and R. Abbott and T. Mulligan and Johnson, {M. L.} and S. Pincus and M. Straume and A. Iranmanesh",
year = "1995",
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TY - JOUR

T1 - Differential impact of age, sex steroid hormones, and obesity on basal versus pulsatile growth hormone secretion in men as assessed in an ultrasensitive chemiluminescence assay

AU - Veldhuis, Johannes D

AU - Liem, A. Y.

AU - South, S.

AU - Weltman, A.

AU - Weltman, J.

AU - Clemmons, D. A.

AU - Abbott, R.

AU - Mulligan, T.

AU - Johnson, M. L.

AU - Pincus, S.

AU - Straume, M.

AU - Iranmanesh, A.

PY - 1995

Y1 - 1995

N2 - A chemiluminescence-based GH assay with 30- to 100-fold increased sensitivity recently disclosed combined basal and pulsatile GH secretion in men. However, how age, sex steroid hormones, and obesity singly and jointly influence the basal vs. pulsatile modes of GH release is not known. We used the foregoing assay (detection threshold, 0.002-0.005 μg/L) and high sensitivity and specificity (≥90% each) deconvolution analysis to quantitate basal and pulsatile GH secretion from 24-h serum GH concentration profiles in 26 healthy lean and obese men, whose ages spanned 18-63 yr and whose percentage body fat ranged from 12-47%. Concentrations of serum insulin-like growth factor I (IGF-I), IGF-I-binding protein-1 (IGFBP-1), and IGFBP-3 were related to specific measures of basal or pulsatile GH release. We observed that mean (24-h) serum GH concentrations embraced a 140-fold range from 0.013-1.8 μg/L and were related negatively to age (r = -0.50; P < 0.01), percentage body fat (r = -0.620; P < 0.01), and their interaction (r = - 0.610; P < 0.01). In contrast, testosterone was a robustly positive statistical determinant of mean serum GH values (r = 0.628; P = 0.0006). Stepwise multivariate regression analysis disclosed that percentage body fat alone and jointly with the serum testosterone concentration controlled, respectively, 38% and 50% of the total variability in GH levels (P = 0.0013 and P = 0.0008). As assessed by deconvolution analysis, GH secretory burst mass was negatively related to percentage body fat (r = -0.621; P < 0.01) and positively to serum testosterone (r = 0.529; P = 0.0054). The calculated half-life of GH correlated positively with serum estradiol (r = 0.447; P = 0.032), and negatively with percentage body fat (r = -0.437; P = 0.048). Basal GH secretion rates were negatively related to serum estradiol (r = - 0.485; P = 0.016). In contrast, GH secretory burst frequency and duration were unrelated to age, percentage body fat, or sex steroids. The fraction of total GH secreted in bursts was negatively correlated with the body mass index (r = -0.540; P < 0.01). Serum IGF-I concentrations were positively related to total pulsatile GH secretion (r = 0.690; P = 0.0011) and negatively to age (r = -0.597; P = 0.007) and percentage body fat (r = - 0.611; P = 0.009). Serum IGFBP-3 was inversely proportional to the basal GH secretion rate (r = -0.467; P = 0.044). In contrast, IGFBP-1 concentrations correlated positively with GH secretory burst mass (r = 0.674; P = 0.0016) as well as basal GH secretion (r = 0.519; P = 0.023), and negatively with age, and percentage body fat and their interactions (absolute r values = 0.517- 0.653; P ≤ 0.021). The serial orderliness of GH release, as assessed by a novel approximate entropy (ApEn) statistic, revealed decreased orderliness (higher ApEn) of GH release with increasing age (r = 0.482; P = 0.019) and adiposity (r = 0.505; P = 0.014). In contrast, the patterned regularity of GH release rose (lower ApEn) with higher serum testosterone concentrations (r = -0.405; P = 0.048). In summary, we infer that in healthy men, 1) basal and pulsatile GH secretion may be regulated differentially by estradiol and testosterone, respectively; 2) basal and pulsatile GH release may influence serum IGF-I, IGFBP-3, and IGFBP-1 concentrations in distinct ways; and 3) the serial regularity or orderliness of GH release is negatively related to age and obesity, but positively to the serum androgen concentration. Accordingly, we hypothesize that 1) distinct neuroendocrine regulatory mechanisms govern basal vs. pulsatile GH secretion; 2) GH target tissue responses, as reflected by serum IGF-I, IGFBP-3, and IGFBP-1 concentrations, are controlled by the specific temporal mode (basal vs. pulsatile) of GH release; and 3) the reproducibility of GH release patterns (estimated by an approximate entropy statistic) in normal men is modulated by key physiological variables (age, body composition, and serum testosterone concentrations), which, therefore, probably act to coordinate hypothalamic somatostatin and GHRH secretion temporally.

AB - A chemiluminescence-based GH assay with 30- to 100-fold increased sensitivity recently disclosed combined basal and pulsatile GH secretion in men. However, how age, sex steroid hormones, and obesity singly and jointly influence the basal vs. pulsatile modes of GH release is not known. We used the foregoing assay (detection threshold, 0.002-0.005 μg/L) and high sensitivity and specificity (≥90% each) deconvolution analysis to quantitate basal and pulsatile GH secretion from 24-h serum GH concentration profiles in 26 healthy lean and obese men, whose ages spanned 18-63 yr and whose percentage body fat ranged from 12-47%. Concentrations of serum insulin-like growth factor I (IGF-I), IGF-I-binding protein-1 (IGFBP-1), and IGFBP-3 were related to specific measures of basal or pulsatile GH release. We observed that mean (24-h) serum GH concentrations embraced a 140-fold range from 0.013-1.8 μg/L and were related negatively to age (r = -0.50; P < 0.01), percentage body fat (r = -0.620; P < 0.01), and their interaction (r = - 0.610; P < 0.01). In contrast, testosterone was a robustly positive statistical determinant of mean serum GH values (r = 0.628; P = 0.0006). Stepwise multivariate regression analysis disclosed that percentage body fat alone and jointly with the serum testosterone concentration controlled, respectively, 38% and 50% of the total variability in GH levels (P = 0.0013 and P = 0.0008). As assessed by deconvolution analysis, GH secretory burst mass was negatively related to percentage body fat (r = -0.621; P < 0.01) and positively to serum testosterone (r = 0.529; P = 0.0054). The calculated half-life of GH correlated positively with serum estradiol (r = 0.447; P = 0.032), and negatively with percentage body fat (r = -0.437; P = 0.048). Basal GH secretion rates were negatively related to serum estradiol (r = - 0.485; P = 0.016). In contrast, GH secretory burst frequency and duration were unrelated to age, percentage body fat, or sex steroids. The fraction of total GH secreted in bursts was negatively correlated with the body mass index (r = -0.540; P < 0.01). Serum IGF-I concentrations were positively related to total pulsatile GH secretion (r = 0.690; P = 0.0011) and negatively to age (r = -0.597; P = 0.007) and percentage body fat (r = - 0.611; P = 0.009). Serum IGFBP-3 was inversely proportional to the basal GH secretion rate (r = -0.467; P = 0.044). In contrast, IGFBP-1 concentrations correlated positively with GH secretory burst mass (r = 0.674; P = 0.0016) as well as basal GH secretion (r = 0.519; P = 0.023), and negatively with age, and percentage body fat and their interactions (absolute r values = 0.517- 0.653; P ≤ 0.021). The serial orderliness of GH release, as assessed by a novel approximate entropy (ApEn) statistic, revealed decreased orderliness (higher ApEn) of GH release with increasing age (r = 0.482; P = 0.019) and adiposity (r = 0.505; P = 0.014). In contrast, the patterned regularity of GH release rose (lower ApEn) with higher serum testosterone concentrations (r = -0.405; P = 0.048). In summary, we infer that in healthy men, 1) basal and pulsatile GH secretion may be regulated differentially by estradiol and testosterone, respectively; 2) basal and pulsatile GH release may influence serum IGF-I, IGFBP-3, and IGFBP-1 concentrations in distinct ways; and 3) the serial regularity or orderliness of GH release is negatively related to age and obesity, but positively to the serum androgen concentration. Accordingly, we hypothesize that 1) distinct neuroendocrine regulatory mechanisms govern basal vs. pulsatile GH secretion; 2) GH target tissue responses, as reflected by serum IGF-I, IGFBP-3, and IGFBP-1 concentrations, are controlled by the specific temporal mode (basal vs. pulsatile) of GH release; and 3) the reproducibility of GH release patterns (estimated by an approximate entropy statistic) in normal men is modulated by key physiological variables (age, body composition, and serum testosterone concentrations), which, therefore, probably act to coordinate hypothalamic somatostatin and GHRH secretion temporally.

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